Angiotensin II is a polypeptide hormone which causes vasoconstriction of the vasculture, stimulates secretion of aldosterone, and induces contraction of renal glomeruli. This hormone plays a role in hypertension, sodium balance, and glomerular function. However, its biochemical mechanism of action is unknown. The possible roles of cyclic 3',5'-nucleotide monophosphates and calcium in the mechanism of glomerular contractility induced by angiotensin II (A II) will be studied. Glomeruli will be isolated intact, but without arterioles, from rat kidneys. Contraction of isolated glomeruli, microscopically measured by the decrease in diameter, will be measured as a function of binding of 125I-A II. Glomerular concentrations of cyclic AMP and cyclic GMP, determined by radioimmunoassays, will be analyzed as a function of binding of A II and glomerular contractility. Measurements of glomerular contractility and cyclic nucleotide levels as function of calcium concentration and in the presence and absence of calcium transport ionophores and blockers will indicate whether or not calcium participates in the mechanism. The relationship of any changes in cyclic nucleotide levels with the glomerular effects of A II will be further evaluated by comparing the glomerular location of A II receptors, determined by autoradiography using 3H-A II, with localization of cyclic nucleotide changes, detected by immunofluorescent cytochemistry. The distribution of A II receptors in isolated glomerular mesangial cells and non-mesangial cells will also be compared with the distribution of enzymes related to cyclic nucleotide metabolism and function. The activities of guanylate cyclase, cyclic GMP phosphodiesterase, cyclic GMP-stimulated protein kinase, and the corresponding cyclic AMP enzymes will be measured. To substantiate that observed changes in cyclic nucleotide levels are related to the action of A II, alteration of glomerular contractility to A II in the presence of phosphodiesterase inhibitors will be examined. In addition, the ability of cyclic nucleotides and their analogues, e.g., (8-p-chlorophenylthio)-cyclic GMP, to mimic the glomerular effect of A II will be determined.